Addressing the ethical issues raised by synthetic human entities with embryo-like features

Abstract

The "14-day rule" for embryo research stipulates that experiments with intact human embryos must not allow them to develop beyond 14 days or the appearance of the primitive streak. However, recent experiments showing that suitably cultured human pluripotent stem cells can self-organize and recapitulate embryonic features have highlighted difficulties with the 14-day rule and led to calls for its reassessment. Here we argue that these and related experiments raise more foundational issues that cannot be fixed by adjusting the 14-day rule, because the framework underlying the rule cannot adequately describe the ways by which synthetic human entities with embryo-like features (SHEEFs) might develop morally concerning features through altered forms of development. We propose that limits on research with SHEEFs be based as directly as possible on the generation of such features, and recommend that the research and bioethics communities lead a wide-ranging inquiry aimed at mapping out solutions to the ethical problems raised by them.DOI: http://dx.doi.org/10.7554/eLife.20674.001

Understanding the Mechanobiology of Early Mammalian Development through Bioengineered Models

“…As such, while characterization efforts are underway (De Bakker et al, 2016;Behjati et al, 2018;Belle et al, 2017;Boroviak et al, 2018), our current understanding of the morphological features of early human development is still based on archival material of dedicated collections (De Bakker et al, 2016;Fujimoto, 2001;Gasser et al, 2014;Hertig et al, 1956), with insights into the signaling dependencies at play often relying on observations made on close primate species (see for example, Boroviak and Nichols, 2017;Nakamura et al, 2016). In vitro models of development may thus currently be our only direct experimental access to the mechanisms regulating patterning, morphogenesis, and mechanobiology in the peri-implantation human embryo, at least until advances in the technical and legal possibilities associated with the in vitro culture of living human embryos (Aach et al, 2017;Deglincerti et al, 2016;Shahbazi et al, 2016). Any assessment about the fidelity to which these systems actually replicate in vivo developmental events may, however, have to await more complete characterization of the embryos they are expected to model, especially given that benchmarks based on mouse biology may not necessarily hold true in human (Blakeley et al, 2015;Boroviak et al, 2018;Rossant and Tam, 2017).…”

In Vitro Microscale Models for Embryogenesis

“…[14] Several research groups have successfully cultured human embryos in vitro within the stipulated 14-day culture rule limit. [15, 16, 17] This rule stipulates restrictions on human embryo research beyond 14 days of development since it involves the primitive streak formation and neural tube development.…”

Human embryo research and the 14-day rule

“…The generation of human embryo-like structures from stem cells in vitro could, of course, itself raise significant ethical issues (Aach et al, 2017;Pera et al, 2015). In many jurisdictions, it is not clear whether these laboratory constructs would be captured under current legislation, owing to the manner in which embryos are defined in law.…”